Immunoglobulin A Antibodies Against Myelin Oligodendrocyte Glycoprotein in a Subgroup of Patients With Central Nervous System Demyelination
Authors: Ana Beatriz Ayroza Galvão Ribeiro Gomes, Laila Kulsvehagen, Patrick Lipps, Alessandro Cagol, Nuria Cerdá-Fuertes, Tradite Neziraj, Julia Flammer, Jasmine Lerner, Anne-Catherine Lecourt, Nina de Oliveira S. Siebenborn, Rosa Cortese, Sabine Schaedelin, Vinicius Andreoli Schoeps, Aline de Moura Brasil Matos, Natalia Trombini Mendes, Clarissa dos Reis Pereira, Mario Luiz Ribeiro Monteiro, Samira Luisa dos Apóstolos-Pereira, Patrick Schindler, Claudia Chien, Carolin Schwake, Ruth Schneider, Thivya Pakeerathan, Orhan Aktas, Urs Fischer, Matthias Mehling, Tobias Derfuss, Ludwig Kappos, Ilya Ayzenberg, Marius Ringelstein, Friedemann Paul, Dagoberto Callegaro, Jens Kuhle, Athina Papadopoulou, Cristina Granziera, Anne-Katrin Pröbstel
Journal: JAMA Neurology (2023)

Differential diagnosis of patients with seronegative demyelinating central nervous system (CNS) disease is challenging. In this regard, evidence suggests that immunoglobulin (Ig) A plays a role in the pathogenesis of different autoimmune diseases. Yet little is known about the presence and clinical relevance of IgA antibodies against myelin oligodendrocyte glycoprotein (MOG) in CNS demyelination.To investigate the frequency of MOG-IgA and associated clinical features in patients with demyelinating CNS disease and healthy controls.This longitudinal study comprised 1 discovery and 1 confirmation cohort derived from 5 centers. Participants included patients with suspected or confirmed demyelinating diseases and healthy controls. MOG-IgA, MOG-IgG, and MOG-IgM were measured in serum samples and cerebrospinal fluid (CSF) of patients, who were assessed from September 2012 to April 2022.Frequency and clinical features of patients who were seropositive for MOG-IgA and double-seronegative for aquaporin 4 (AQP4) IgG and MOG-IgG.After the exclusion of 5 participants with coexisting AQP4-IgG and MOG-IgA, MOG-IgG, and/or MOG-IgM, 1339 patients and 110 healthy controls were included; the median follow-up time was 39 months (range, 0-227 months). Of included patients with isolated MOG-IgA, 11 of 18 were female (61%), and the median age was 31.5 years (range, 3-76 years). Among patients double-seronegative for AQP4-IgG and MOG-IgG (1126/1339; 84%), isolated MOG-IgA was identified in 3 of 50 patients (6%) with neuromyelitis optica spectrum disorder, 5 of 228 patients (2%) with other CNS demyelinating diseases, and 10 of 848 patients (1%) with multiple sclerosis but in none of the healthy controls (0/110). The most common disease manifestation in patients seropositive for isolated MOG-IgA was myelitis (11/17 [65%]), followed by more frequent brainstem syndrome (7/16 [44%] vs 14/75 [19%], respectively; P = .048), and infrequent manifestation of optic neuritis (4/15 [27%] vs 46/73 [63%], respectively; P = .02) vs patients with MOG-IgG. Among patients fulfilling 2017 McDonald criteria for multiple sclerosis, MOG-IgA was associated with less frequent CSF-specific oligoclonal bands (4/9 [44%] vs 325/351 [93%], respectively; P < .001) vs patients with multiple sclerosis who were MOG-IgG/IgA seronegative. Further, most patients with isolated MOG-IgA presented clinical attacks after recent infection or vaccination (7/11 [64%]).In this study, MOG-specific IgA was identified in a subgroup of patients who were double-seronegative for AQP4-/MOG-IgG, suggesting that MOG-IgA may be a novel diagnostic biomarker for patients with CNS demyelination.